This 3-year study will characterize and investigate the transmission dynamics of Trypanosoma cruzi in the southern United States. This parasite is a significant cause of mortality in Latin America. In the US, human cases are rare, but infections in wildlife are common. Characterizing US isolates will aid in understanding the natural history of T. cruzi which could lead to better ways of prevention in endemic areas. [unreadable] [unreadable] Trypanosoma cruzi, causative agent of Chagas disease (American trypanosomiasis), is a significant cause of mortality in Latin America. There are five published reports of autochthonous cases of Chagas disease in the United States; however, there are numerous reports of natural T. cruzi infection of wildlife, exotic, and domestic animals. Our long-range goal is to understand the risk factors that conspire to allow maintenance of T. cruzi in nature and ultimately its transmission to people. As our first objective in pursuit of this goal, we propose to characterize strains of T. cruzi from United States (US) hosts. Our central hypothesis is that different T. cruzi genetic strains will have distinct transmission cycles and these strains will have variable biologic characteristics. The rationale behind the proposed study is that understanding the transmission cycles of genetic variants and infection dynamics of T. cruzi within the vertebrate hosts and vectors is an essential part of revealing the mechanisms by which this parasite is maintained in nature. To accomplish this objective, we will pursue four specific aims: (1) investigate transmission cycles of US T. cruzi genetic types among reservoirs, (2) compare the in vitro growth characteristics of genetically classified clones of US T. cruzi isolates, (3) compare vectoral capacity of Triatoma sanguisuga for US and exotic virulent isolates of T. cruzi, and (4) determine infection dynamics and pathogenicity of US T. cruzi isolates for laboratory mice, raccoons, and opossums. Our expectations are that, at the conclusion of this 3-year study, we will have elucidated many of the predominate genetic types of T. cruzi circulating in the US, determined if host-parasite genetic type association exists, characterized the growth characteristics of numerous US T. cruzi isolates, shown that a local Triatoma species can vector exotic virulent isolates of T. cruzi, and determined the infectivity and pathogenicity of selected US T. cruzi isolates for experimentally infected mammals. These data will aid in understanding the epidemiology of T. cruzi in the US by providing data on what genetic types currently circulate in the US and will aid in understanding relative risk of human infection by understanding the virulence of T. cruzi isolates obtained from different transmission cycles. The proposed study incorporates multiple opportunities for undergraduate, graduate, and veterinary students to obtain biomedical research experience. [unreadable] [unreadable] [unreadable]